Application of physiologically based pharmacokinetic modeling in setting acute exposure guideline levels for methylene chloride.

Acute exposure guideline levels (AEGLs) are derived to protect the human population from adverse health effects in case of single exposure due to an accidental release of chemicals into the atmosphere. AEGLs are set at three different levels of increasing toxicity for exposure durations ranging from 10 min to 8 h. In the AEGL setting for methylene chloride, specific additional topics had to be addressed. This included a change of relevant toxicity endpoint within the 10-min to 8-h exposure time range from central nervous system depression caused by the parent compound to formation of carboxyhemoglobin (COHb) via biotransformation to carbon monoxide. Additionally, the biotransformation of methylene chloride includes both a saturable step as well as genetic polymorphism of the glutathione transferase involved. Physiologically based pharmacokinetic modeling was considered to be the appropriate tool to address all these topics in an adequate way. Two available PBPK models were combined and extended with additional algorithms for the estimation of the maximum COHb levels. The model was validated and verified with data obtained from volunteer studies. It was concluded that all the mentioned topics could be adequately accounted for by the PBPK model. The AEGL values as calculated with the model were substantiated by experimental data with volunteers and are concluded to be practically applicable.

Engineering controls for furniture strippers to meet the OSHA methylene chloride PEL.

This case study demonstrates how methylene chloride exposures during furniture stripping can be reduced to below the Occupational Safety and Health Administration (OSHA) permissible exposure limit (PEL) of 25 ppm (as an 8-hour time-weighted average). Five surveys were conducted at one facility; the first four resulted in employee exposure geometric means from 39 to 332 ppm. For the fifth survey local exhaust ventilation was used at the stripping tank and the rinsing area, which together exhausted 138 m3/min (4860 ft3/min). Additional controls included providing adequate make-up air, adding paraffin wax to the stripping solution, raising the level of the stripping solution in the tank, and discussing good work practices with the employee. The employees' methylene chloride exposures during the fifth survey resulted in a geometric mean of 5.6 ppm with a 95% upper confidence limit of 8.3 ppm, which was found to be significantly lower than the OSHA PEL and the OSHA action level of 12.5 ppm. The cost of the ventilation system was $8900.

A simplified HPTLC screening method for the estimation of the PAH content in soil samples.

Based on a highly significant correlation between the visual fluorescing fraction of PAH on the one hand and the total EPA-PAH16 content in mineral soils on the other hand, a deliberately incomplete RP-TLC separation of these compounds into a few fingerprint-like compressed bands within a determined "PAH window" has been achieved. The resulting band-pattern does not interfere normally with the more or less non-polar phenolic compounds which are associated with natural soil humic substances. The extraction step has been extremely simplified with regard to the quantity of the soil sample and of the extractant. The accuracy of this procedure has been ascertained by means of recovery experiments with an artificial soil enriched with PAH. A single spot application mode and an evaluation scheme allow the estimation of EPA-PAH16 contents of soil samples in relation to threshold values (1 or 5 or 10 mg/kg). This HPTLC screening method has been compared against standard HPLC methods. The simplified extraction step and the separation by HPTLC minimizes the actual costs and the time spent per sample.